The overarching goal of this Mid-Career Investigator Award in HIV-related Patient-Oriented Research (K- 24) application is to make meaningful contributions to social and behavioral science research aimed at improving HIV treatment outcomes in sub-Saharan Africa. My specific goals are to 1) mentor students, post- doctoral fellows, and junior faculty in social-behavioral HIV research who will 2) conduct patient-based research to improve antiretroviral therapy adherence in a rural African setting. My mentoring activities will be primarily based at Mbarara University of Science and Technology (MUST) in Mbarara, Uganda, and Harvard University in Cambridge, Massachusetts. The mentoring program will leverage research and teaching infrastructure at these universities and will consist of direct one-on-one mentoring in the conduct of social-behavioral HIV research, as well as formal seminars on research methods, manuscript writing, and grant writing. A mentoring advisory committee will formally evaluate mentored junior investigators, on the basis of their productivity. The research program will test the feasibility of preventing antiretroviral therapy interruptions through novel real-time wireless adherence monitoring. This new direction is based on our finding that incomplete adherence, to the extent that it occurs in rural Uganda, is manifested as treatment interruptions due to structural and/or economic barriers to treatment access. We found that the duration of treatment interruption for patients on non-nucleoside reverse transcriptase inhibitor antiretroviral therapy is directly related to the risk of virologic rebound. While an interruption of 4 days poses little risk of virologic rebound, an interruption of 15 days poses a 50% risk of virologic rebound. These data suggest that there is a 3-5 day window to intervene after missed doses but before virologic failure. Because adherence is so closely associated with viral suppression, accurate adherence monitoring can provide a strategy to strategically limit viral RNA monitoring only to those patients at a defined risk for viral rebound. Novel wireless adherence monitoring tools combined with the well developed wireless communications network in many Sub-Saharan African countries creates the potential for a new paradigm of HIV treatment defined by strategic viral RNA monitoring and the proactive prevention rather than the reactive response to virologic failure. PUBLIC HEALTH RELEVANCE: While there has been encouraging data on treatment adherence in sub-Saharan Africa, treatment options remain limited. Treatment success will require sustained adherence over decades of treatment. Novel approaches to adherence monitoring and intervention, as well as a strong cadre of investigators to build behavioral science research infrastructure, will help design effective, feasible, and culturally relevant antiretroviral adherence interventions to promote optimal HIV treatment response in sub-Saharan Africa.